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Ortiz-Ibez et al.

World Journal of Surgical Oncology (2015)3:6


DOI 10.1186/s12957-015-0622-6

WORLD JOURNAL OF
SURGICAL ONCOLOGY

RESEARCH

Open Access

Surgical resection of massive liposarcomas


at the extremities: a 10-year experience in a
referral musculoskeletal sarcoma unit
Brbara Ortiz-Ibez1,2, Jos V. Amaya3, Francisco Baixauli3, Manuel Angulo3, Empar Mayordomo-Aranda4
and Carlos Barrios2*

Abstract
Background: There is still no consensus regarding the management of patients with massive liposarcomas located
in the extremities. Several discrepancies related to the aggressiveness of the surgery and the application of
concomitant radiotherapy and chemotherapy treatments remain controversial. The purpose of this study was to
analyse the clinicopathological characteristics, prognostic factors and outcomes of a series of patients with massive
liposarcomas of the extremities who were treated at a referral hospital specializing in musculoskeletal oncology.
Methods: This was an observational, descriptive and retrospective case series covering 10 years of clinical practice.
The records of 26 adults, 14 men and 12 women, with localized massive liposarcomas in the extremities were
studied. The average age was 53 years. The patients were treated from January 2003 until January 2012. Wide
surgical resections with limb-sparing surgeries were performed for most patients (96.2 %).
Results: The average tumour size was 15.1 6.8 cm in the greatest dimension. Regarding the histological subtypes,
there were 11 well-differentiated or atypical lipomatous tumours (42.3 %), 10 myxoid (38.5 %) and 5 (19.2 %) round
cell and pleomorphic liposarcomas. Regarding the malignancy grades, 19 cases (73 %) were classified as low grade.
Among these low-grade tumours predominated the well-differentiated subtype (57.9 %). Within high-grade tumours,
the round cell and pleomorphic subtype was most frequent (57.1 %; p = 0.011). Radiotherapy was additionally applied
to 12 patients (46.2 %) and adjuvant chemotherapy to 5 (19.3 %). Tumour recurrence was observed in only 2 cases
(7.7 %). Only 1 of these cases developed lung metastatic dissemination.
Conclusions: Across the entire series, these massive tumours did not compromise the survival of the patients. The
histologic subtype and the malignancy degree were closely related. Proper and early diagnosis and therapeutic
management of these patients via the application of wide-margin surgical excision are essential to ensure long-term
survival.
Keywords: Liposarcoma, Massive tumour size, Soft tissue sarcomas, Wide surgical excision

Background
Liposarcoma is one of the most common soft tissue sarcomas in adults, accounting for approximately 10 to
30 % of these tumours [1, 2]. Up to 80 % of liposarcomas
involve the lower extremities, and these tumours are primarily deep seated in the proximal aspect of the thigh
[3]. The risks of recurrence and metastatic dissemination
* Correspondence: carlos.barrios@ucv.es
2
Institute for Research on Musculoskeletal Disorders, Valencia Catholic
University, Quevedo 2, 46001 Valencia, Spain
Full list of author information is available at the end of the article

have been related to the histologic malignancy grade and


tumour size [3, 4].
Based on morphological and cytogenetic aberrations,
liposarcomas are commonly classified into four subtypes:
well-differentiated, dedifferentiated, myxoid and pleomorphic with round cells [5]. The well-differentiated
and dedifferentiated subtypes represent 43 and 16 % of
all liposarcomas, respectively, and are most frequently
located in the retroperitoneum. The myxoid and the
pleomorphic with round cell subtypes account for 29
and 12 % of liposarcomas, respectively, and most often

2015 Ortiz-Ibez et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution
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Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

affect the extremities [5]. The myxoid type exhibits an


intermediate malignant behaviour and predominately occurs in adults and in the lower extremities, particularly
the thighs, buttocks and the popliteal fossae. The round
cell and pleomorphic variants are typically aggressive
and often develop metastatic dissemination [69]. Most
cases appear in adults over the age of 50 years and without a sex predilection [6, 810].
All subtypes are associated with a high risk of local recurrence unless they are properly excised [11]. The welldifferentiated subtype can be separated from the other
four types because of its lowest recurrence rate and
much better prognosis [8]. The recurrence rates range
from 5 to 83 % depending on the histologic subtype and
location [5]. Regarding prognostic factors, both pathology and tumour size are extremely valuable. In a large
series of 418 cases, the percentage of round cells and the
tumour diameter were directly correlated with increased
risks of metastases and death [4]. The importance of the
histological subtype has been emphasized in a recent review in which the pathologic characteristics were found
to be the main predictor of death from sarcoma [12].
Therefore, the four subgroups of liposarcoma exhibit different natures and patterns of behaviour [5, 11, 13, 14].
Patients with well-differentiated liposarcomas at the
extremities usually present with a painless, slowly growing soft mass, which can be accurately delineated with
magnetic resonance imaging (MRI) [15, 16]. The extremity lesions have the potential to hold locally aggressive behaviour, but with no metastatic potential unless
they dedifferentiate [17]. Based on these different clinical
behaviours, it has been proposed that the term atypical
lipomatous tumour should be used instead of well-differentiated liposarcoma.
Clinical presentations with lung metastases, advanced
age and large tumour sizes are associated with poor
prognoses [18, 19]. However, regarding tumour size, appropriate wide surgical resections seem to decrease the
recurrence rate to near 0 even for massive tumours [20].
A comparison of two clinical trials seeking to determine
the prognostic factors for tumour progression revealed
that lesions localized to the extremities are associated
with favourable prognoses in young people, and adjuvant
chemotherapy results in a greater relapse-free survival
only in patients older than 30 [21].
The primary treatment for high-risk patients is surgical
resection and local control with adjuvant radiotherapy
[2225]. The resection of local recurrences localized to
the extremities can provide results that are similar to
those of primary tumour resection. In cases of unresectable pulmonary metastases or extrapulmonary metastatic
sarcomas, the prognoses are very unfavourable, and systemic chemotherapy is required. In these cases, surgery
might be considered as a palliative treatment [5, 26, 27].

Page 2 of 10

There is still no consensus regarding the management


of patients with massive liposarcomas located in the extremities. Several discrepancies related to the aggressiveness of the surgery and the application of concomitant
radiotherapy and chemotherapy treatments remain
controversial.
Initially, patients with well-differentiated liposarcomas
in the extremities are expected to have a better chance
of being cured; therefore, wide excision should be the
initial therapy of choice. Even in cases with lesions in
contact with major nerves or blood vessels, conservative
resection preserving these critical structures and the
limb function has proved to be highly effective in terms
of low recurrence and metastatic spreading [17].
Given this knowledge background, the current study
aimed to analyse a series of patients with massive liposarcomas of the extremities who were treated at a referral tertiary hospital with a specialized musculoskeletal
oncologic unit. The clinicopathological characteristics,
the prognostic factors and the outcomes were reviewed.
To our knowledge, this study is innovative given the limited literature that has been published regarding massive
liposarcomas.

Methods
This was a retrospective, observational and descriptive
study of a series of cases. We analysed a total of 26 patients, with a mean age of 53 years (15.6 SD), who were
diagnosed with liposarcoma in the extremities. Patients
ages ranged from 27 to 86 years. Of the 26 patients studied, there were 14 males (mean age 56.8 17.5 SD) and
12 females (mean age 48.5 12.3 SD). The time of
follow-up was calculated from the date of the surgical
treatment. The median follow-up period was 38.5 months
(13.5 SD).
This study was based on data from the medical records that were registered from January 2003 to December 2012. Data from patients who received any of the
following types of treatment were collected: limb-saving
surgery (25 cases), radical surgery with amputation
(1 case), adjuvant radiotherapy (8 patients), adjuvant
chemotherapy (1 case) and combined radiotherapy with
chemotherapy (4 cases). All patients were treated in a
musculoskeletal oncology unit of a tertiary referral hospital. Written informed consent was obtained from the
patients for the publication of this report.
Data regarding age, sex, histological diagnosis, malignancy grade, topographic location, tumour size, clinical
comorbidities, metastasis, surgical treatment, concomitant therapy, local recurrence and clinical situation were
collected from the medical records.
Regarding the clinical symptoms, most of the patients
presented with a palpable mass; however, in a single patient, the tumour was incidentally discovered in the

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

context of an iliac ischemic process. At the time of patients referral, 20 presented with primary lesions and six
patients had been previously operated and were referred
with recurrent masses. The main comorbidities were
several cardiovascular risk factors.
The predominant tumour location was the thigh (20
patients). The other 6 patients presented with tumours
in different locations: 2 were in the arm, 2 were in the
upper posterior thigh involving the posterior pelvic muscles and 2 were in the knee.
Across the entire series, 19 cases (73 %) were labelled
as low-grade malignancies (19 cases, grade I). Among
the remaining 7 cases with high-grade tumours, 5 were
labelled as grade II and 2 were labelled as grade III.
The statistical analyses of the data were initially performed with descriptive calculations of frequencies and
percentages for the qualitative variables. The means,
standard deviations and minimum and maximum values
were also obtained for the quantitative measurements.
These analyses were conducted across the whole sample.
Patients were also segregated in subsamples by sex,
histologic subtype and tumour size. Fishers exact tests
with contingency tables were applied to assess differences between groups. Differences were considered statistically significant when p < 0.05.

Results
According to age and grade, the patient distribution consisted of 9 low-grade and 4 high-grade cases in patients
below the age of 50 years. Among the patients older
than 50 years, there were 10 low-grade and 3 high-grade
cases. Regarding the histological diagnoses, there was a
clear tendency toward specific histological types according to sex; the well-differentiated type predominated in
males (57.1 %), and the myxoid form predominated in
the women (58.3 %; Table 1).
Among the low-grade tumours, the well-differentiated
histologic subtype was most common (11 of 19 cases);
among the high-grade tumours, the predominant histological type was the round and/or pleomorphic cell type
(4 of 7 cases; p = 0.011). The well-differentiated histological type was never classified as high grade. The myxoid type exhibited a similar ratio of cases in both groups
(Table 2). In some cases, various liposarcoma subtypes
were mixed; these cases were classified according the
most dominant variant (Figs. 1 and 2).
The surgical treatments consisted of wide resections of
the tumours with limb-preserving techniques in 25 cases
(96.2 %; Fig. 3). All lesions involving or adjacent to
major nerves or blood vessels were marginally resected
with careful dissection of these critical structures. The
sciatic nerve and the femoral and the popliteal arteries
were preserved in all patients with lower-extremity lesions. In the two patients with upper-arm lesions, the

Page 3 of 10

Table 1 Histologic characteristics and locations of the


liposarcomas according to gender
Males

Females

n (%)

n (%)

Histologic type
Well-differentiated

8 (57, 1)

3 (25)

Myxoid

3 (21, 4)

7 (58, 3)

Round cell and pleomorphic cells

3 (21, 4)

2 (16, 7)

High-grade

10 (71, 4)

9 (75)

Low-grade

4 (28, 6)

3 (25)

Arm

1 (7, 1)

1 (8, 3)

Thigh

10 (71, 4)

10 (83, 3)

Upper posterior thigh and gluteal muscles

1 (7, 1)

1 (8, 3)

Knee

2 (14, 3)

Grade

Location

The percentages in parentheses indicate the proportion of cases within the


category. There were no differences between males and females in the
histologic characteristics and tumour location according to Fishers exact test

mean peripheral nerve trunk nerves and the major arteries (brachial and radial) were also preserved.
Only 1 case required amputation of the limb (3.8 %);
this patient was diagnosed in the context of an iliac ischemia. The distribution of concomitant therapies according to the degree of tumour malignancy revealed
Table 2 Age, histologic subtype, location and metastatic
development according to the degree of malignancy
Low-grade

High-grade

n (%)

n (%)

50

9 (47, 4)

4 (57, 1)

>50

10 (52, 6)

3 (42, 9)

Well-differentiated

11 (57, 9)

Myxoid

7 (36, 8)

3 (42, 9)

Round and/or pleomorphic cells

1 (5, 3)

4 (57, 1)

Age (years)

Histologic type

p < 0.05
Location
Arm

2 (28, 6)

Thigh

15 (78, 9)

5 (71, 4)

Upper posterior thigh and gluteal muscles

2 (10, 5)

Knee

2 (10, 5)

M1

1 (14, 3)

M0

19 (100)

6 (85, 7)

Metastases

The percentages in parentheses indicate the proportion of cases within the


category. Fishers exact test was used for statistical analysis

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

Page 4 of 10

Fig. 1 Myxoid liposarcoma. a Abundant small cells, very few mature adipocytes and necrotic areas. Haematoxylin-eosin (HE) 30 m. b Detail of a rather
myxoid area, with scattered atypical adipocytes, lipoblasts and small round cells in a bluish myxoid background with typical delicate neoformed vessels
(HE, 60 m)

some relevant features, i.e. 52.6 % of the low-grade tumours and 42.9 % of the high-grade did not receive any
treatment other than surgery. Radiotherapy was added
to surgery for 31.6 % of the low-grade and 28.6 % of the
high-grade tumours (Figs. 3 and 4). Chemotherapy as a
single associated treatment was administered only to a
single low-grade case. Finally, the combination of radiotherapy and chemotherapy was applied to the same
number of patients in each group according to the degree of malignancy (Table 3).
Across the entire series, the mean tumour size as measured following the surgical removal of the specimens
was 15.1 6.8 cm in the greatest diameter. Comparison
of the sizes of the tumours across gender revealed that

the tumour sizes of the men were slightly larger than


those of the women (16.0 7.3 in men and 14.2 6.3 cm
in women), but this difference was not significant due to
the large dispersion of results, particularly in the men.
However, the proportion of women who exhibited small
tumours (15 cm) was 75 % (9 of the 12 women), while
only 1 woman had a large tumour (8.3 %; p = 0.074;
Fig. 5).
At the last follow-up, 24 patients continued to be disease free without any loss of limb function. There were
only two local recurrences, and both occurred in women
younger than 50. Only 1 patient presented with metastases that were located in the lungs. This woman had a
high-grade pleomorphic and round cell liposarcoma

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

Page 5 of 10

Fig. 2 Dedifferentiated liposarcoma. a Dense highly pleomorphic sarcomatoid areas intermixed with low-grade liposarcoma adipose subtype (HE,
12 m). b Areas of low-grade liposarcoma, adipose subtype, with atypical adipocytes in fibrous septa intermixed with mature adipocytes and lipoblasts
(HE, 60 m)

Fig. 3 Distribution of concomitant therapy according to the degree


of malignancy

located in the upper arm. This was the case in the study
that evolved to death, which occurred 9 months after
the diagnosis (Fig. 6). The association between the development of metastasis and the evolution to death was
statistically significant (p = 0.038). According to these
data, the final local control rate was 92.3 %.
One of the two grade III cases died due to the tumour;
thus, the survival in this group was 50 % (Fig. 7a). One
of the four cases with a pleomorphic variant progressed
to death; thus, the survival curves segregated by histological type revealed that the survival in these cases was
75 % (Fig. 7b).

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

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Fig. 4 A 69-year-old male with myxoid liposarcoma grade II located in the rectus muscle of the left thigh. a Preoperative MRI, December 2008;
b clinical appearance; c intraoperative aspect during surgical resection of the tumour; and d excised tumour part measuring 22 15 cm. This
patient received adjuvant radiotherapy

Table 3 Applied treatments and clinical evolution according to


gender
Total

Males

Females

n (%)

n (%)

n (%)

Only surgical excision

13 (50)

8 (57, 1)

5 (41, 7)

Radiotherapy

8 (30, 8)

4 (28, 6)

4 (33, 3)

Discussion
The strength of this study lies in the inclusion of a series
of patients with massive lower-extremity liposarcomas
from a referral musculoskeletal oncology unit of a tertiary
hospital. The sample might be therefore representative of

Concomitant therapy

Chemotherapy

1 (3, 8)

1 (8, 3)

Radiotherapy + chemotherapy

4 (15, 4)

2 (14, 3)

2 (16, 7)

Yes

2 (7, 7)

2 (16, 7)

No

24 (92, 3)

14 (100)

10 (83, 3)

Local recurrence

Metastases
M1

1 (3, 8)

1 (8, 3)

M0

25 (96, 2)

14 (100)

11 (91, 7)

The percentages in parentheses indicate the proportion of cases within the


category. There were no differences between males and females in the
applied therapy and in the clinical course according to the Fishers exact test

Fig. 5 Tumour size by gender segregated by tumour sizes 15


and >15 cm in average maximum diameter

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

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Fig. 6 A 53-year-old female with grade III round cell pleomorphic liposarcoma (highly malignant) located in the triceps muscle of the left upper arm.
a Resonance angiography showing an increase in tumour vascularization; b preoperative MRI, January 2007; c clinical appearance of the palpable mass;
and d intraoperative appearance. The tumour measured 15 9 8 cm. This patient developed lung metastases and died 9 months after the diagnosis

liposarcomas with large clinical effects. Both the age and


sex distributions matched with those in the literature related to smaller liposarcomas [5, 8].
In this series, the well-differentiated histological pattern was the most common in men and the myxoid form
was the most common in women, in accordance with
the results of previous studies [5, 8, 28, 29]. Regarding
the degrees of tumour malignancies, low-grade neoplasms predominated among the well-differentiated type.
Among the high-grade tumours, the round and/or pleomorphic cell type was the most common. The prevalence of the myxoid type was similar in the low- and
high-grade groups. In this series, low-grade massive liposarcomas were found to be more than twice as frequent
as their highly malignant counterparts.
In the current review, the tumours were predominantly
localized to the proximal portion of the thigh, which
agrees with previous studies [3, 12]. Because only these tumours were examined in the current study, the proportions of retroperitoneal tumours and other liposarcoma

areas are unknown. The clinical presentation was a palpable mass in all cases. No pain was present upon presentation, but pain has been reported to be the first symptom
in one third of cases in the literature [5, 30].
The differences in various clinical behaviours have
generated confusion about the best way to clinically treat
soft tissue sarcomas. Surgical tumour resection has been
proposed to be the most effective treatment for soft
tissue sarcomas [8, 11, 25]. Regarding liposarcomas,
complete surgical excision in association with radiation
offers the best local control [31, 32]. This therapeutic approach has been specifically proposed as the treatment
of choice for the well-differentiated and myxoid subtypes [33]. The local recurrence rates reported in the
literature only about extremity lesions range from 8 to
52 % [3436]. In our series, the local recurrence rate
was only 7.7 %, which is below the lower range of those
reported previously.
In the current study focussed on massive liposarcoma
at the extremities, all of the patients underwent wide

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

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Fig. 7 Survival (months) in relation to the malignancy grade (a) and the histological subtype (b) (January 2003December 2012)

resections of the tumours. In half of the cases, no additional treatments were applied. When the distribution
of concomitant treatments was analysed according to
the degree of malignancy of the tumour, some findings
that deserved comment were revealed. As in other large
series of soft tissue liposarcomas, radiotherapy was applied to one third of the patients with low-grade
tumours and applied to a smaller proportion of the
high-grade cases [3].
In a study conducted by Zagars et al. [33], the indication
for chemotherapeutic therapy was a tumour size >5 cm. It
has also been reported that myxoid liposarcomas exhibit

good responses to chemotherapy [28]. However, according


to the currently available literature, it is reasonable to include chemotherapy as a part of the treatment strategy for
these tumours only in patients with untreated, advanced
unresectable disease and patients with metastatic liposarcomas. In our series, chemotherapy was applied to 5 cases,
2 of which were low-grade cases and 3 were high-grade
tumours. One of these 5 cases was a well-differentiated
liposarcoma, 1 was a pure myxoid tumour, 2 were myxoid
tumours with round cells and 1 was a pleomorphic liposarcoma. The scheme of surgery plus radiotherapy and/or
chemotherapy was applied to the same number of patients

Ortiz-Ibez et al. World Journal of Surgical Oncology (2015)3:6

in each group depending on the degree of malignancy.


These data indicate that the addition of neoadjuvant
chemotherapy or radiotherapy in this series did not follow the current recommendations for soft tissue sarcomas [21].
Local recurrence has been strongly associated with
metastatic disease in soft tissue sarcomas [37]. In this
study, local recurrence was only observed in two patients after being treated in the orthopaedic oncologic
unit. However, a total of 6 patients underwent a revision
surgery due to insufficient surgical margins in the initial
surgery, performed outside the orthopaedic oncologic
unit in 5 of theses cases. These findings are inconsistent
with the proposals of other authors [18, 21] in terms of
prognostic factors. The two cases with local recurrence
did not meet the accepted criteria for bad prognoses;
both of these cases were under 50 years old and appeared as de novo liposarcomas, and the histological
subtypes were myxoid. In the current series, surgical resection of local recurrences of massive liposarcomas in
the extremities produced results that were similar to
those of the resection of the primary tumours because
both of these patients are currently alive. The promising
results of this series cannot be related to the high number of well-differentiated liposarcomas treated, because
only 11 out of 26 patients (42 %) were identified.
In the current series, the average tumour size exceeded
15 cm; thus, the sample was divided into two groups
based on whether the tumour was larger or smaller than
15 cm. Traditionally, the size limit used to discriminate
large and small tumours has been 10 cm [3, 5]. This
series exclusively included patients from a referral hospital. Therefore, the great majority of the tumours were
massive and advanced in their evolutions. In our system,
small liposarcomas have previously been treated in
county primary hospitals. Therefore, large tumour size
per se could not be analysed as a prognostic factor.
Only 1 patient with a high-grade pleomorphic round
cell liposarcoma developed metastases that were located
in the lungs. This patient was the only case in the study
who exhibited an unfavourable evolution that led to
death due to tumour spread. This case confirms the reported experience that has described lower survivorship
of the pleomorphic variant and the presence of distant
metastases as the major cause of death in patients with
liposarcomas [29, 33]. Although a history of prior local
recurrence and a positive resection margin significantly
affected the prognoses of the patients, in the series of
Zagras et al. [33], histologic subtype was the most important factor.
The study has some obvious limitations due to the nature of clinical reviews. Patients under 18 years of age
were not included; therefore, the results cannot be extrapolated to adolescent and paediatric patients. However, the

Page 9 of 10

prevalence of liposarcomas in patients below the age of 18


is very small [1, 38]; thus, this limitation will affect only a
small fraction of cases. Furthermore, the retrospective nature of this study implies that, in some cases, not all of the
analysed parameters were included in the patient medical
records. Although this information is systematically computerized in our institution, some of the oldest cases
lacked surgery-related information and were consequently
eliminated from the study. Another limitation is that the
majority of the patients were referred from other hospitals, and some of them underwent previous operations.
This feature complicated the collection of the clinical
characteristics of the primary tumours from the medical
records.

Conclusions
In conclusion, wide excision surgery produces excellent
results in the treatment of massive liposarcomas of the
extremities in terms of not only low recurrence rate but
also good limb function. Only 1 patient died of metastases. The results from series were highly satisfactory, although improvements in the criteria for the application
of coadjuvant chemotherapy and radiotherapy would be
desirable in the future.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
CB and FB assisted with the design of the study and revised the final version
of the manuscript. BOI performed the data collection and drafted the
manuscript. FB, JVA and MA performed the surgeries. EMA was the
pathologist revising all histologic diagnosis. CB performed the statistical
analysis and coordinated the whole study. All authors read and approved
the final manuscript.
Acknowledgements
There are no acknowledgements to be made with regard to this study.
Author details
1
Department of Orthopedic Surgery, Hospital de Sagunto, Valencia, Spain.
2
Institute for Research on Musculoskeletal Disorders, Valencia Catholic
University, Quevedo 2, 46001 Valencia, Spain. 3Musculoskeletal Sarcoma Unit,
La Fe University and Technologic Hospital, Valencia, Spain. 4Department of
Pathology, La Fe University and Technologic Hospital, Valencia, Spain.
Received: 7 April 2015 Accepted: 11 June 2015

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